Vanderbilt Clinical Trials

Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

Purpose

This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. The study contains a Safety Lead-in Phase in which the safety and tolerability of encorafenib + binimetinib + cetuximab will be assessed prior to the Phase 3 portion of the study.

Condition

BRAF V600E-mutant Metastatic Colorectal Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Age ≥ 18 years at time of informed consent - Histologically- or cytologically-confirmed CRC that is metastatic - Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory - Progression of disease after 1 or 2 prior regimens in the metastatic setting - Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1 - Adequate bone marrow, cardiac, kidney and liver function - Able to take oral medications - Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential - Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up

Exclusion Criteria

Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other epidermal growth factor receptor (EGFR) inhibitors - Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks - Symptomatic brain metastasis or leptomeningeal disease - History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes) - Known history of acute or chronic pancreatitis - History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization - Uncontrolled blood pressure despite medical treatment - Impaired GI function or disease that may significantly alter the absorption of encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption) - Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy - History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli - Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) - Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy - Known history of HIV infection - Active hepatitis B or hepatitis C infection - Known history of Gilbert's syndrome - Known contraindication to receive cetuximab or irinotecan at the planned doses

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Safety Lead-in, Triplet Arm	Encorafenib + binimetinib + cetuximab.	Drug: Encorafenib Orally, once daily. Drug: Binimetinib Orally, twice daily. Drug: Cetuximab Standard of care.
Experimental Doublet Arm	Encorafenib + cetuximab.	Drug: Encorafenib Orally, once daily. Drug: Cetuximab Standard of care.
Active Comparator Control Arm	Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.	Drug: Cetuximab Standard of care. Drug: Irinotecan Standard of care. Drug: Folinic Acid Standard of care. Other names: FA Drug: 5-Fluorouracil Standard of care. Other names: 5-FU

More Details

Status: Completed
Sponsor: Pfizer

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.